title: Early thymus and activation-regulated chemokine (TARC) reduction and response following panobinostat treatment in patients with relapsed/refractory Hodgkin lymphoma following autologous stem cell transplant.
abstract: Abstract In a phase 2 trial of panobinostat in 129 patients with relapsed or refractory Hodgkin lymphoma, exploratory analyses of chemokines and cytokines were prospectively performed in 109 patients to determine their association with clinical outcomes. Patients were categorized into two groups (reductions > median and reductions ≤ median) based on percentage change from baseline of log10 transformed measurements. Thymus and activation-regulated chemokine (TARC) was most strongly associated with clinical outcome. Early reduction of TARC was observed in responding patients, with the greatest reduction at cycle 1, day 15 (C1D15). Of 93 patients with C1D15 samples, there were three complete and 25 partial responses. The group with TARC reductions > median at C1D15 had more responders (18 [39%] vs. 10 [21%]), longer progression-free survival (10.6 vs. 4.9 months), shorter time to response and longer overall survival than the group with reductions ≤ median. This study is registered at www.ClinicalTrials.gov , NCT00742027.
authors.affiliation: Sir Peter MacCallum Department of Oncology, University of Melbourne , Parkville, Victoria , Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Harrison
authors.forename: Andy K
authors.initials: AK
authors.lastname: Hsu
authors.forename: Paul
authors.initials: P
authors.lastname: Neeson
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.forename: Martha
authors.initials: M
authors.lastname: Li
authors.forename: Paula
authors.initials: P
authors.lastname: Savage
authors.forename: Roberto
authors.initials: R
authors.lastname: Bugarini
authors.forename: Denise
authors.initials: D
authors.lastname: Williams
authors.forename: Margaret
authors.initials: M
authors.lastname: Squier
authors.forename: David S
authors.initials: DS
authors.lastname: Ritchie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D054414:Chemokine CCL17 / Q000097:blood*; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D000077767:Panobinostat; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D054414:Chemokine CCL17; D006877:Hydroxamic Acids; D007211:Indoles; D016212:Transforming Growth Factor beta; D000077767:Panobinostat